FDA Approves CABOMETYX® (Cabozantinib) for Advanced Neuroendocrine Tumors, Expanding Treatment Options
Exelixis, Inc. has announced that the U.S. Food and Drug Administration (FDA) has approved CABOMETYX® (cabozantinib) for the treatment of adult and pediatric patients aged 12 years and older with previously treated, unresectable, locally advanced, or metastatic well-differentiated pancreatic neuroendocrine tumors (pNET) and extra-pancreatic neuroendocrine tumors (epNET). Neuroendocrine tumors (NET) are heterogeneous malignancies that arise from neuroendocrine cells within the digestive tract and other organs, such as the lungs and pancreas. Many patients with advanced NET face a poor prognosis due to limited treatment options and disease progression.
Significance of FDA Approval
Dr. Jennifer Chan, M.D., M.P.H., Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute, emphasized the importance of this milestone:
“The characteristics of NET vary widely from patient to patient, and very few treatment options have demonstrated the ability to improve outcomes across such a heterogeneous population. It was encouraging to see that cabozantinib resulted in significant delays in disease progression in the CABINET trial—regardless of primary tumor site and grade. This FDA approval marks a meaningful advancement, which may establish an important new treatment option for patients, without limitations based on somatostatin receptor expression and functional status.”
This latest approval marks the sixth FDA approval for CABOMETYX and is based on data from the phase 3 CABINET trial, a pivotal study evaluating cabozantinib versus placebo in two distinct cohorts of previously treated NET patients: those with advanced pNET and those with advanced epNET.
The final progression-free survival (PFS) results were presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine. In early 2025, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors to include cabozantinib as a category 1 preferred regimen for most well-differentiated advanced NET following specific treatments, and as a category 2A preferred regimen for other forms of advanced NET based on tumor grade and prior therapy requirements.
CABINET Trial and Clinical Findings
The phase 3 CABINET trial provided robust clinical evidence for the efficacy of CABOMETYX in previously treated NET patients. The study demonstrated a statistically significant improvement in PFS for both cohorts. Key findings include:
- A notable delay in disease progression regardless of primary tumor site and grade.
- A significant clinical benefit compared to placebo in patients with both pancreatic and extra-pancreatic NET.
- A manageable safety profile, consistent with previous studies of cabozantinib in other tumor types.
Dr. Amy Peterson, M.D., Executive Vice President of Product Development & Medical Affairs and Chief Medical Officer at Exelixis, expressed the company’s commitment to improving treatment options for NET patients:
“As a company committed to improving the standard of care for people living with advanced, difficult-to-treat cancers, we are proud to bring CABOMETYX to patients with previously treated advanced neuroendocrine tumors. I would like to extend our sincere gratitude to the Alliance for Clinical Trials in Oncology for conducting the CABINET trial, to the FDA for their collaboration on the review of this application, and to all the patients and physicians who participated in this important study. Looking forward, we are doubling down on our commitment to the NET community as we prepare to initiate our STELLAR-311 pivotal trial examining zanzalintinib versus everolimus in the first half of 2025.”
Safety Profile and Considerations
The safety profile observed in the CABINET trial was consistent with previous data on CABOMETYX. No new safety signals were identified. However, a higher incidence of hypertension was noted in NET patients compared to those with other approved tumor types. The majority of patients required dose modifications or reductions to manage treatment-related adverse events. As a tyrosine kinase inhibitor (TKI), cabozantinib’s known side effects include fatigue, diarrhea, hypertension, and palmar-plantar erythrodysesthesia (hand-foot syndrome). Physicians are encouraged to monitor patients closely and adjust doses as needed to maintain tolerability.
Impact on the Neuroendocrine Tumor Community
Cindy Lovelace, co-founder of The Healing NET Foundation, shared her perspective on how the approval of CABOMETYX brings new hope to NET patients:
“As a person who has lived with neuroendocrine tumors for over 14 years—and who has met many patients and caregivers in that time—I know that there are many challenges that come with this diagnosis, including the need to closely monitor the disease and adapt your treatment approach if faced with progression. As very few targeted therapies have been approved for advanced NET in recent years, I am excited that CABOMETYX brings new hope to the patients in our community who have been in need of effective new treatment options.”
This FDA approval represents a significant advancement for patients with previously treated advanced NET, expanding their therapeutic options and potentially improving survival outcomes. Exelixis remains committed to supporting the NET community and advancing research efforts, with upcoming studies, including STELLAR-311, set to further explore innovative treatments for this challenging disease.
As Exelixis continues to develop novel therapies for difficult-to-treat cancers, the approval of CABOMETYX for advanced NET highlights the potential of targeted therapies in managing rare and heterogeneous malignancies. The company’s ongoing research underscores its dedication to enhancing the standard of care and improving long-term outcomes for patients with neuroendocrine tumors.
